Ephedrine for Childbirth

Recruiting at 1 trial location

Overseen By Daniel Katz, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Icahn School of Medicine at Mount Sinai

Disqualifiers: Hypertension, Pre-eclampsia, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

135 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a small dose of Ephedrine can reduce certain heart rate issues in babies during childbirth when mothers receive a specific type of pain relief. The focus is on preventing a common, non-diagnostic fetal heart rate pattern called Category II tracing, which might cause concerns during labor. Ephedrine is known to raise heart rate and blood pressure and has been safely used in childbirth for years, though not specifically for this purpose. Women requesting pain relief during labor and who have a normal baby heart rate pattern before the procedure might be suitable for this trial. As a Phase 4 trial, this study involves an FDA-approved treatment and aims to understand how Ephedrine can benefit more patients during labor.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What is the safety track record for ephedrine?

Past studies have safely used ephedrine in pregnant women. It prevents low blood pressure during spinal anesthesia without causing major problems for the mother or baby. Research has shown that ephedrine does not increase the risk of birth defects or miscarriages. However, repeated use might reduce the body's responsiveness, which doctors consider when treating patients.

This trial uses a lower amount of ephedrine than typically given to manage low blood pressure, suggesting it should be well-tolerated. Overall, ephedrine has a long history of safe use in pregnant women, so it is expected to be safe in this study as well. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using ephedrine for childbirth because it acts quickly to counteract low blood pressure, a common side effect of epidurals during labor. Unlike standard treatments like phenylephrine, which primarily constrict blood vessels, ephedrine works by stimulating the heart to increase blood flow, potentially providing more stable blood pressure control. This quick response can be crucial for ensuring both mother and baby remain safe and comfortable during delivery.

What evidence suggests that ephedrine might be an effective treatment for category II fetal heart rate tracings?

In this trial, participants will receive either ephedrine or a placebo to assess its effectiveness during childbirth. Research has shown that ephedrine can prevent low blood pressure during spinal anesthesia for C-sections, helping to maintain stable blood pressure with anesthesia. By raising heart rate and blood pressure, ephedrine may also improve blood flow to the uterus. However, some studies have found that ephedrine might cause fetal acidosis, where the baby's blood becomes too acidic, in certain cases. Despite this, ephedrine has been safely used in childbirth care for over 50 years, demonstrating a strong safety record in this area. ^{3 4 6 7 8}

Who Is on the Research Team?

James Leader

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for women aged 18-55 years in labor who want pain relief and can give informed consent. They must have a reassuring 'Category I' fetal heart rate before getting anesthesia. Women with suspected pre-eclampsia, non-reassuring 'Category II or III' fetal heart rates, or a history of high blood pressure cannot participate.

Inclusion Criteria

Requesting labor analgesia

Able to provide informed written consent

I am a woman aged between 18 and 55.

Exclusion Criteria

I have a history of high blood pressure.

Suspected pre-eclampsia

I have chosen not to receive spinal or epidural anesthesia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ephedrine or placebo after combined spinal epidural anesthesia to study its effects on fetal heart rate tracing and blood pressure

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including blood pressure and heart rate changes

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Ephedrine
• Normal Saline Placebo

Trial Overview The study tests if giving ephedrine before combined spinal epidural anesthesia can prevent certain changes in the baby's heart rate and mother's blood pressure during childbirth. Ephedrine has been used safely for over 50 years but its preventive use here is new.

How Is the Trial Designed?

Group I: Ephedrine Experimental Treatment 1 Intervention

3 minutes after the placement of a combined spinal epidural with 25 mcg fentanyl, 7.5 mg ephedrine IV will be administered to the patient, 12 minutes later, a second dose of 7.5mg will be administered to the patient as long as the patient is not hypertensive (BP no greater than 140/90)

Group II: Placebo Placebo Group 1 Intervention

3 minutes after the placement of a combined spinal epidural with 25 mcg fentanyl, 2.5cc 0.9% NS IV will be administered to the patient, 12 minutes later, a second dose of , 2.5cc 0.9% NS will be administered to the patient.

Ephedrine is already approved in United States, Canada for the following indications:

Approved in United States as Ephedrine for:

• Hypotension
• Bronchial asthma
• Narcolepsy
• Myasthenia gravis
• Allergic disorders

Approved in Canada as Ephedrine for:

• Nasal decongestant
• Asthma
• Bronchitis

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Published Research Related to This Trial

The Ephedra-Gypsum herb-pair demonstrated significant antipyretic effects in a study with 30 male Wistar rats, effectively reducing yeast-induced fever in a dose-dependent manner.

In an ovalbumin-induced asthmatic model with 36 male SD rats, Ephedra-Gypsum extracts improved asthma symptoms by reducing eosinophil counts and lung weight ratios, indicating its potential as an effective treatment for bronchial asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antipyretic and anti-asthmatic activities of traditional Chinese herb-pairs, Ephedra and Gypsum. Mei, F., Xing, XF., Tang, QF., et al.[2018]

Ephedrine, a stimulant found in Ephedra-based weight-loss products, has been linked to serious adverse reactions such as stroke, heart attacks, and seizures, prompting health authorities in Canada to recall certain products.

Reports of milder side effects like palpitations and insomnia have also been noted, leading to a reevaluation of the safety of Ephedra-containing products in the Netherlands.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ephedrine and ephedra in weight loss products and other preparations]. van der Hooft, CS., Stricker, BH.[2013]

The study found that the herbal combination of Herba Ephedrae and Radix Aconiti Lateralis (Mahuang-Fuzi) has a complex distribution of alkaloids in various rat tissues, indicating potential therapeutic effects but also risks of side effects due to the accumulation of certain alkaloids, particularly hypaconitine.

While the combination showed lower bioavailability and higher clearance for some alkaloids compared to single-herb extracts, it also resulted in prolonged residence time for aconitum alkaloids, raising concerns about potential intoxication and the need for further investigation into its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative tissue distribution and excretion study of alkaloids from Herba Ephedrae-Radix Aconiti Lateralis extracts in rats. Ren, M., Song, S., Liang, D., et al.[2017]

The study investigated how different ratios of the Mahuang-Guizhi herb-pair affect the bioavailability of five ephedrine alkaloids in rats, revealing significant differences in pharmacokinetic parameters like plasma concentration and half-life.

These findings suggest that adjusting the ratios of Mahuang and Guizhi can optimize the therapeutic effects while potentially reducing toxicity, paving the way for improved formulations in treating conditions like asthma and cough.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic comparisons of five ephedrine alkaloids following oral administration of four different Mahuang-Guizhi herb-pair aqueous extracts ratios in rats. Wei, P., Huo, HL., Ma, QH., et al.[2019]

The study investigated the pharmacokinetics of 11 alkaloids from the Mahuang-Fuzi combination and found that these alkaloids had slower elimination rates in plasma compared to single-herb extracts, indicating a longer mean residence time and potential for accumulation with continuous use.

Given the potential cardiovascular and central nervous system risks associated with the alkaloids in this herbal combination, the findings suggest that careful drug monitoring is necessary to ensure safe usage of Mahuang-Fuzi in treating conditions like colds and rheumatic arthralgia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous quantification and pharmacokinetics of alkaloids in Herba Ephedrae-Radix Aconiti Lateralis extracts. Song, S., Tang, Q., Huo, H., et al.[2017]

Ma-huang extracts contain additional toxins beyond ephedrine, which contributes to their overall cytotoxicity, indicating that not all harmful effects can be attributed to ephedrine alone.

Grinding the herb significantly increases its toxicity, and boiling the whole herb for two hours can help create an extract with a better balance of ephedrine to toxins, potentially making it safer for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytotoxicity assessment of Ma-huang (Ephedra) under different conditions of preparation. Lee, MK., Cheng, BW., Che, CT., et al.[2022]

Ephedrae herba, a traditional Chinese herb, contains over 281 chemical constituents, with alkaloids and volatile oils being the most bioactive, and is used for treating conditions like colds and bronchial asthma.

While Ephedrae herba has multiple pharmacological effects, including anti-inflammatory and anti-viral properties, it can cause adverse reactions if overused, highlighting the importance of adhering to a maximum dosage of 10 g.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ephedrae herba: A comprehensive review of its traditional uses, phytochemistry, pharmacology, and toxicology. Zheng, Q., Mu, X., Pan, S., et al.[2023]

Ephedrine and pseudoephedrine are the primary alkaloids found in various species of Chinese Ephedra, with significant variations in their concentrations depending on the specific plant species studied.

Certain species, like Ephedra sinica and E. intermedia var. tibetica, have higher total alkaloid contents, while others, such as E. przewalskii and E. lepidosperma, contain negligible amounts of alkaloids, making them unsuitable for medicinal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Quality evaluation of twelve species of Chinese Ephedra (ma huang)]. Zhang, JS., Tian, Z., Lou, ZC.[2017]

Samples of Ephedra sinica collected from arid environments exhibited anatomical features such as a sinuous epidermis and increased fiber bundles, which are associated with higher quality.

These arid samples also contained greater amounts of total ephedrine alkaloids and pseudoephedrine, suggesting that the best quality Ephedra Herb should be sourced from drier regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Studies of Ephedra plants in Asia. Part 6: Geographical changes of anatomical features and alkaloids content of Ephedra sinica. Wang, LL., Kakiuchi, N., Mikage, M.[2021]

Citations

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The Effects of Intravenous Ephedrine During Spinal ... Our findings demonstrated that prophylactic intravenous ephedrine during spinal anesthesia for cesarean section can prevent hypotension without significant ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02062801

Prophylactic Ephedrine and Combined Spinal Epidurals for ... Outcomes Data collected will include the incidence of profound early fetal bradycardia as previously defined; lowest and highest BP in first 30 minutes; ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10016133/

The Effect of Painless Delivery with Intrathecal Sufentanil ... This study investigated the effect of intrathecal sufentanil for painless delivery on labor progress and neonatal outcomes in 1,055 pregnant ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1743919118316856

Review Phenylephrine vs ephedrine in cesarean delivery ... Phenylephrine and ephedrine were both effective in maintaining hemodynamic balance. Newborns benefited more from phenylephrine in elective cesarean delivery.

5. researchgate.net researchgate.net/publication/11298660_Effectiveness_of_Intravenous_Ephedrine_Infusion_during_Spinal_Anaesthesia_for_Caesarean_Section_Based_on_Maternal_Hypotension_Neonatal_Acid-base_Status_and_Lactate_Levels

Effectiveness of Intravenous Ephedrine Infusion during ... We observed an unexpectedly high incidence of fetal acidosis with ephedrine and found evidence that longer spinal-delivery intervals increase ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK547661/

Ephedrine - StatPearls - NCBI Bookshelf - NIH Ephedrine is a medication used to manage and treat clinically significant hypotension. It is in the sympathomimetic class of drugs.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2020/213407Orig1s000lbl.pdf

213407Orig1s000 | FDA Data indicate that repeated administration of ephedrine can result in tachyphylaxis. Be aware of this possibility when treating anesthesia- ...

8. reference.medscape.com reference.medscape.com/drug/akovaz-corphedra-ephedrine-342436

Akovaz, Corphedra (ephedrine) dosing, indications, ... ... data of use in pregnant females have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal ...